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1.
Huan Jing Ke Xue ; 43(1): 500-509, 2022 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-34989535

RESUMO

The residual content of organochlorine pesticides (OCPs) in soil and crops of typical agricultural land in the southern Leizhou peninsula were determined using gas chromatography-mass spectrometry (GC-MS). Additionally, the bioconcentration factors of organochlorine pesticides in eight crops were investigated, and the human health risk was evaluated. The results indicated that 10 types of OCPs were detected to varying degrees; HCHs and heptachlor were the main OCPs in the study area, with the residual contents of 23.83-111.51 ng·g-1 and 11.01-25.97 ng·g-1 in soil and 7.54-61.28 ng·g-1 and 3.96-30.97 ng·g-1 in crops, respectively. A small number of soil and crop samples were found to exceed the standard. The ratio of α-HCH/γ-HCH was less than 1 in 87.50% of the soil samples, and ß-HCH/α-HCH was larger than 1. This indicates that the HCHs were probably derived from the recent use of lindane and historical residual pollution, whereas the heptachlor was mainly derived from underground insect pests and the application of termite control agents. The enrichment ability of OCPs was significantly different among different crops. The bioaccumulation capacity of vegetables was higher than that of fruit. Furthermore, bulb vegetables (leeks) were significantly stronger than other vegetables. A human health risk assessment of OCPs showed that OCP-combined pollution would not cause significant health risks to the population in the study area. However, the maximum value of HI in some crop samples was greater than 1, indicating that there were still potential risks, which should not be ignored.


Assuntos
Hidrocarbonetos Clorados , Praguicidas , Poluentes do Solo , China , Monitoramento Ambiental , Humanos , Hidrocarbonetos Clorados/análise , Praguicidas/análise , Medição de Risco , Solo , Poluentes do Solo/análise
2.
Plant J ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35020972

RESUMO

Developing seed depends on sugar supply for its growth and yield formation. Maize produces the largest grains among cereals. However, there is a lack of holistic understanding on the transcriptional landscape of genes controlling sucrose transport to, and utilization within, maize grains. By performing in-depth data-mining of spatial-temporal transcriptomes coupled with histological and heterologous functional analyses, we identified transporter genes specifically expressed in the maternal-filial interface, including (i) ZmSWEET11/13b in the placento-chalazal where sucrose was exported into the apoplasmic space, and (ii) ZmSTP3, ZmSWEET3a/4c (monosaccharide transporters), ZmSUT1, ZmSWEET11/13a (sucrose transporters) in the basal endosperm transfer cells for retrieval of apoplasmic sucrose or hexoses after hydrolysis by extracellular invertase. In embryo and its surrounding regions, an embryo-localized ZmSUT4 and a cohort of ZmSWEETs were specifically expressed. Interestingly, drought repressed those ZmSWEETs likely exporting sucrose but enhanced the expression of most transporter genes for uptake of apoplasmic sugars. Importantly, this drought-induced fluctuation in gene expression was largely attenuated by an increased C supply via controlled pollination, indicating that the altered gene expression is conditioned by C availability. Based on the analyses above, we proposed a holistic model on the spatial-temporal expression of genes that likely govern sugar transport and utilization across maize maternal and endosperm and embryo tissues during the critical stage of grain set. Collectively, the findings represent an advancement towards a holistic understanding of the transcriptional landscape underlying post-phloem sugar transport in maize grain and indicate that the drought-induced changes in gene expression is attributable to low C status.

3.
J Psychiatr Res ; 147: 59-66, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35026594

RESUMO

The effects of gene-by-environment (G×E) interactions on complex diseases are significant, especially the superimposed effects of multiple environmental factors. However, research on the multi-environments-gene interactions of anxiety, depression, and self-harm is still limited. This study included white individuals (N = 66,041-74,482) from the UK Biobank. We fitted all environmental factors to a single environmental score (ES), and the estimated ES was used to calculate the multiplicative interaction effects between ES and genome-wide SNPs. Heritability was stratified by minor allele frequency (MAF) and linkage disequilibrium (LD). Our research found 10 loci with significant interaction effects, such as rs114830993 (PRICKLE2, P = 2.30 × 10-8), rs151323364 (ASTN2, P = 2.71 × 10-10) and rs536631793 (SYN3, P = 4.09 × 10-8). In addition, we found that G×E heritability has a significant contribution to the depression of Patient Health Questionnaire-9 (PHQ-9) scores (h2G×E (female) = 6.1%, h2G×E (male) = 8.7%). Our research supported the important influence of multi-environments-gene interactions on anxiety, depression, and self-harm and provided clues for the prevention and etiological research of them.

4.
Small ; : e2107371, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35018710

RESUMO

A joint theoretical and experimental study is reported to systematically explore over a library of transition metal-silicon intermetallics for understanding silicon-controlled active site motifs and discovering hydrogen-evolving electrocatalysts. On the one hand, every low-index surface termination of 115 transition metal (M)-silicon (Si) intermetallics is enumerated, followed by cataloging of stable adsorption sites and prediction of catalytic activities on the main exposed facets. It is theoretically found that silicon atoms in silicon-rich structures (especially MSi2 and MSi) show a strong site-isolating effect, which can eliminate M-M-M hollow and M-M bridge sites with too strong hydrogen-binding ability and thereby provide great opportunities for the exposure of novel highly active sites (e.g., M-top and Si-related sites). On the other hand, solid-state redox reactions are developed to synthesize a set of 24 silicides containing 5 MSi, 13 MSi2 , and 6 others, most of which are phase-pure samples. The experimental studies demonstrate that too rich silicon content in silicides (e.g., MSi2 ) leads to adverse effects, such as the formation of amorphous SiOx layers on the silicide surface, masking the presence of active sites during electrocatalysis. Finally, 5 MSi (M = Rh, Pd, Pt, Ru, Ir) as highly active hydrogen-evolving electrocatalysts are identified.

5.
Mol Med Rep ; 25(1)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34850958

RESUMO

Corilagin is the primary active component of the Euphorbia phyllanthus plant and has significant anti­cancer properties. However, the biological effects and mechanisms of corilagin on acute myeloid leukemia (AML) have not been clarified. The Cell Counting Kit­8 and Carboxyfluorescein Diacetate Succinimidyl Ester assay results showed that corilagin significantly inhibited proliferation of the AML cell line HL­60 in a time­ and dose­dependent manner. Western blotting and flow cytometry analysis were performed to determine the levels of apoptosis in HL­60 cells. The protein levels of cleaved caspase­3 and Bak were upregulated, while Bcl­xl was downregulated in cells treated with corilagin. The percentage of early­ and late­stage apoptotic cells increased following corilagin treatment in a dose­dependent manner, indicating that the intrinsic mitochondrial apoptosis pathway was activated by corilagin. Simultaneously, western blotting and immunofluorescence results revealed that autophagy was suppressed; this was accompanied by a decrease in light chain 3­II (LC3­II) conversion and autophagosomes. MicroRNA (miRNA/miR) profile analysis showed that corilagin elevated the expression of the tumor suppressor miR­451, while the mRNA and protein levels of high mobility group protein B1 (HMGB1), the target of miR­451, decreased following exposure to corilagin. Knockdown of miR­451 decreased the downregulation of HMGB1 caused by corilagin, indicating negative regulation of HMGB1 by miR­451 during corilagin treatment. Furthermore, knockdown of miR­451 also attenuated corilagin­induced proliferation inhibition of HL­60 cells, implying that miR­451 was essential for the proliferation inhibitory effect of corilagin. In conclusion, these results indicated that corilagin induced apoptosis and inhibited autophagy in HL­60 cells by regulating the miR­451/HMGB1 axis, and corilagin may be a novel therapeutic drug for the treatment of AML.

6.
Pharmgenomics Pers Med ; 14: 1537-1547, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34876832

RESUMO

Introduction: Genetic variability in genes encoding drug-metabolizing enzymes may contribute to the heterogeneity of drug responses in different populations. Extensive research in pharmacogenomics in major populations around the world provides us with a great deal of information about drug-related genetic polymorphisms. Objective: The purpose of this study was to detect the genetic variation of drug-metabolism-related genes in the five ethnic minorities Daur, Hezhen, Ewenki, Mongolian and Manchu in China, and to analyze the distribution differences among ethnic groups. Methods: We genotyped 32 SNPs of drug metabolism genes in 882 healthy Chinese volunteers from five ethnic groups. The genotype frequency and allele frequency of the five ethnic groups were calculated, and the different variants among the five ethnic groups were compared by chi-square test. Genetic parameters were analyzed using Popgene software. The genetic structure of five ethnic minorities was analyzed by principal component analysis, and compared with 26 populations. Results: We found that SNPs of genes related to drug metabolism existed diversity in different populations. Among them, rs8192766 and rs9419082 in CYP2E1 showed statistical differences between Daur and Manchu, and NAT2 rs1801280 showed statistical differences between Hezhen and Mongolian. In addition, the five populations we studied had the smallest differences with EAS populations. There was haplotype diversity in CHST3, VKORC1, CYP1A2 and CYP2E1 genes in the five ethnic minorities, and these haplotype polymorphisms were related to the use of corresponding drug doses. Cluster analysis shows that the five ethnic minorities in Heilongjiang Province are clustered together with the EAS populations. Conclusion: These results suggest that understanding the diversity of drug-related genetic markers is critical for individualized drug gene therapy programs in ethnic minorities in China as well as in populations highly mixed with these ethnic groups.

7.
Quant Imaging Med Surg ; 11(12): 4781-4796, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34888189

RESUMO

Background: Local failure (LF) following chemoradiation (CRT) for head and neck cancer is associated with poor overall survival. If machine learning techniques could stratify patients at risk of treatment failure based on baseline and intra-treatment imaging, such a model could facilitate response-adapted approaches to escalate, de-escalate, or switch therapy. Methods: A 1:2 retrospective case control cohort of patients treated at a single institution with definitive radiotherapy for head and neck cancer who failed locally, in-field at a primary or nodal structure were included. Radiomic features were extracted from baseline CT and CBCT scans at fractions 1 and 21 (delta) of radiotherapy with PyRadiomics and were selected for by: reproducibility (intra-class correlation coefficients ≥0.95), redundancy [maximum relevance and minimum redundancy (mRMR)], and informativeness [recursive feature elimination (RFE)]. Separate models predicting LF of primaries or nodes were created using the explainable boosting machine (EBM) classifier with 5-fold cross-validation for (I) clinical only, (II) radiomic only (CT1 and delta features), and (III) fused models (clinical + radiomic). Twenty-five iterations were performed, and predicted scores were averaged with a parallel ensemble design. Receiver operating characteristic curves were compared between models with paired-samples t-tests. Results: The fused ensemble model for primaries (using clinical, CT1, and delta features) achieved an AUC of 0.871 with a sensitivity of 78.3% and specificity of 90.9% at the maximum Youden J statistic. The fused ensemble model trended towards improvement when compared to the clinical only ensemble model (AUC =0.788, P=0.134) but reached significance when compared to the radiomic ensemble model (AUC =0.770, P=0.017). The fused ensemble model for nodes achieved an AUC of 0.910 with a sensitivity of 100.0% and specificity of 68.0%, which also trended towards improvement when compared to the clinical model (AUC =0.865, P=0.080). Conclusions: The fused ensemble EBM model achieved high discriminatory ability at predicting LF for head and neck cancer in independent primary and nodal structures. Although an additive benefit of delta radiomics over clinical factors could not be proven, the results trended towards improvement with the fused ensemble model, which are promising and worthy of prospective investigation in a larger cohort.

8.
Front Genet ; 12: 722421, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868201

RESUMO

Clear cell renal cell carcinoma (ccRCC) is widely acknowledged to be extremely sensitive to immunotherapy, emphasizing the tremendous impacts on which the tumor microenvironment (TME) has shown. However, the molecular subgroups characterized by the TME features scarcely serve as the risk stratification guides in clinical practice for survival outcomes and immunotherapy response prediction. This study generated fresh insights into a novel TME-related prognostic signature derived from The Cancer Genome Atlas database using integrated bioinformatics analyses. Subsequently, Kaplan-Meier survival analysis, receiver operating characteristic analysis, and univariate and multivariate Cox regression analysis were performed to evaluate and validate the efficacy and the accuracy of the signature in ccRCC prognosis. Furthermore, we discovered that the risk score presented an increased likelihood of correlation with miscellaneous clinicopathological characteristics, natural killer cell-mediated cytotoxicity, immune cell infiltration levels, and immune checkpoint expression. These findings highlighted the notion that the six-gene signature characterized by the TME features may have implications on the risk stratification for personalized and precise immunotherapeutic management.

9.
J Am Chem Soc ; 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34870982

RESUMO

The first total syntheses of bisdehydrotuberostemonine D (8) and putative bisdehydrotuberostemonine E (9), two novel pyrrole Stemona alkaloids, along with the synthesis of bisdehydrotuberostemonine (3) have been completed in 12-13 steps. Our strategy harnesses the power of transition-metal-catalyzed reactions employing Ir, Ru, and Pd, in particular Ir-catalyzed asymmetric allylation of aldehydes, two distinct protocols recently developed by Carreira and Krische, respectively. The threefold use of Ir catalysis, first in the stereodivergent construction of two contiguous stereocenters at C (9,10) and then in rapid formation of the two γ-butyrolactone motifs, enabled the route's efficiency. Through this work, the originally assigned structure of bisdehydrotuberostemonine E (9) should be revised as 18α-bisdehydrotuberostemonine D (8*).

11.
Materials (Basel) ; 14(23)2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34885623

RESUMO

Bile duct injury (BDI) and bile tract diseases are regarded as prominent challenges in hepatobiliary surgery due to the risk of severe complications. Hepatobiliary, pancreatic, and gastrointestinal surgery can inadvertently cause iatrogenic BDI. The commonly utilized clinical treatment of BDI is biliary-enteric anastomosis. However, removal of the Oddi sphincter, which serves as a valve control over the unidirectional flow of bile to the intestine, can result in complications such as reflux cholangitis, restenosis of the bile duct, and cholangiocarcinoma. Tissue engineering and biomaterials offer alternative approaches for BDI treatment. Reconstruction of mechanically functional and biomimetic structures to replace bile ducts aims to promote the ingrowth of bile duct cells and realize tissue regeneration of bile ducts. Current research on artificial bile ducts has remained within preclinical animal model experiments. As more research shows artificial bile duct replacements achieving effective mechanical and functional prevention of biliary peritonitis caused by bile leakage or obstructive jaundice after bile duct reconstruction, clinical translation of tissue-engineered bile ducts has become a theoretical possibility. This literature review provides a comprehensive collection of published works in relation to three tissue engineering approaches for biomimetic bile duct construction: mechanical support from scaffold materials, cell seeding methods, and the incorporation of biologically active factors to identify the advancements and current limitations of materials and methods for the development of effective artificial bile ducts that promote tissue regeneration.

12.
Front Cell Dev Biol ; 9: 722953, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858970

RESUMO

Mesenchymal stromal cells (MSCs) show potential for treating preclinical models of newborn bronchopulmonary dysplasia (BPD), but studies of their therapeutic effectiveness have had mixed results, in part due to the use of different media supplements for MSCs expansion in vitro. The current study sought to identify an optimal culture supplement of umbilical cord-derived MSCs (UC-MSCs) for BPD therapy. In this study, we found that UC-MSCs cultured with human platelet lysate (hPL-UCMSCs) were maintained a small size from Passage 1 (P1) to P10, while UC-MSCs cultured with fetal bovine serum (FBS-UCMSCs) became wide and flat. Furthermore, hPL was associated with lower levels of senescence in UC-MSCs during in vitro expansion compared with FBS, as indicated by the results of ß-galactosidase staining and measures of senescence-related genes (CDKN2A, CDKN1A, and mTOR). In addition, hPL enhanced the proliferation and cell viability of the UC-MSCs and reduced their doubling time in vitro. Compared with FBS-UCMSCs, hPL-UCMSCs have a greater potential to differentiate into osteocytes and chondrocytes. Moreover, using hPL resulted in greater expression of Nestin and specific paracrine factors (VEGF, TGF-ß1, FGF2, IL-8, and IL-6) in UC-MSCs compared to using FBS. Critically, we also found that hPL-UCMSCs are more effective than FBS-UCMSCs for the treatment of BPD in a rat model, with hPL leading to improvements in survival rate, lung architecture and fibrosis, and lung capillary density. Finally, qPCR of rat lung mRNA demonstrated that hPL-UCMSCs had lower expression levels of inflammatory factors (TNF-α and IL-1ß) and a key chemokine (MCP-1) at postnatal day 10, and there was significant reduction of CD68+ macrophages in lung tissue after hPL-UCMSCs transplantation. Altogether, our findings suggest that hPL is an optimal culture supplement for UC-MSCs expansion in vitro, and that hPL-UCMSCs promote lung repair in rat BPD disease.

13.
Diabetol Metab Syndr ; 13(1): 141, 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34863268

RESUMO

BACKGROUND: The involvement of circular RNAs (circRNAs) in diabetic nephropathy (DN) has been gradually identified. In this study, we aimed to explore the functions of circRNA F-box/WD repeat-containing protein 12 (circ-FBXW12) in DN development. METHODS: Reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay was performed for the levels of circ-FBXW12, FBXW12 mRNA, microRNA-31-5p (miR-31-5p) and Lin-28 homolog B (LIN28B) mRNA. RNase R assay was used to analyze the stability of circ-FBXW12. Cell Counting Kit-8 (CCK-8) assay, flow cytometry analysis and 5-ethynyl-2'- deoxyuridine (EdU) assay were employed to evaluate cell viability, cell cycle and proliferation, respectively. Enzyme linked immunosorbent assay (ELISA) was done to measure the concentrations of inflammatory cytokines. Western blot assay was conducted for protein levels. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were examined with commercial kits. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the relationships among circ-FBXW12, miR-31-5p and LIN28B. RESULTS: Circ-FBXW12 level was increased in DN patients' serums and high glucose (HG)-induced human mesangial cells (HMCs). Circ-FBXW12 knockdown suppressed cell proliferation, arrested cell cycle, reduced extracellular matrix (ECM) production and oxidative stress in HG-induced HMCs. Circ-FBXW12 was identified as the sponge for miR-31-5p, which then directly targeted LIN28B. MiR-31-5p inhibition reversed circ-FBXW12 knockdown-mediated effects on cell proliferation, cell cycle process, ECM production and oxidative in HG-triggered HMCs. Moreover, miR-31-5p overexpression showed similar results with circ-FBXW12 knockdown in HG-stimulated HMC progression, while LIN28B elevation reversed the effects. CONCLUSION: Circ-FBXW12 knockdown suppressed HG-induced HMC growth, inflammation, ECM accumulation and oxidative stress by regulating miR-31-5p/LIN28B axis.

14.
Zhen Ci Yan Jiu ; 46(11): 958-62, 2021 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-34865334

RESUMO

OBJECTIVE: To investigate the effect of electroacupuncture combined with thunder-fire moxibustion on urodynamics in patients with neurogenic bladder (NB) after spinal cord injury(SCI). METHODS: A total of 60 patients with NB after SCI were divided into control group and observation group using a random number table, with 30 patients in each group. Bladder management protocol was performed for both groups. The patients in the control group were given electroacupuncture at Shangliao (BL31), Zhongliao (BL33), Xialiao (BL34), and Ciliao (BL32) at both sides, and those in the observation group were given thunder-fire moxibustion as mild-warm moxibustion at Yaoyangguan (GV3), Mingmen (CV4), Qihai (CV6), Guanyuan (CV4), and Zhongji (CV3) in addition to the treatment in the control group; electroacupuncture or moxibustion was performed for 20 min each time, once a day, with 10 times as one course of treatment, and both groups were treated for 3 courses. Number of times of voluntary urination, maximum single urine volume, and number of times of urethral catheterization were recorded at 3 d before and after treatment; maximum urinary flow rate during urination, maximum bladder capacity during urination, bladder pressure during the bladder filling period, and residual urine volume were recorded before and after treatment, and bladder compliance was calculated; clinical outcome was evaluated for both groups. RESULTS: After treatment, both groups had significant reductions in the numbers of times of urination and urethral catheterization (P<0.05) and a significant increase in maximum single urine volume (P<0.05), and the observation group had significantly better results than the control group (P<0.05). After treatment, both groups had significant reductions in residual urine volume and bladder pressure during the bladder filling period, and the observation group had significantly greater reductions than the control group (P<0.05); both groups had significant increases in bladder compliance, maximum bladder capacity during urination, and maximum urinary flow rate during urination, and the observation group had significantly higher values than the control group (P<0.05). The observation group had a significantly higher response rate than the control group ï¼»90.00% (27/30) vs 63.33% (19/30), P<0.05ï¼½. CONCLUSION: Thunder-fire moxibustion combined with electroacupuncture can effectively improve bladder urodynamics and has a marked clinical effect in patients with NB after SCI.

15.
Bioengineered ; 12(2): 12461-12469, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34931923

RESUMO

Severe mortality due to the COVID-19 pandemic resulted from the lack of effective treatment. Although COVID-19 vaccines are available, their side effects have become a challenge for clinical use in patients with chronic diseases, especially cancer patients. In the current report, we applied network pharmacology and systematic bioinformatics to explore the use of biochanin A in patients with colorectal cancer (CRC) and COVID-19 infection. Using the network pharmacology approach, we identified two clusters of genes involved in immune response (IL1A, IL2, and IL6R) and cell proliferation (CCND1, PPARG, and EGFR) mediated by biochanin A in CRC/COVID-19 condition. The functional analysis of these two gene clusters further illustrated the effects of biochanin A on interleukin-6 production and cytokine-cytokine receptor interaction in CRC/COVID-19 pathology. In addition, pathway analysis demonstrated the control of PI3K-Akt and JAK-STAT signaling pathways by biochanin A in the treatment of CRC/COVID-19. The findings of this study provide a therapeutic option for combination therapy against COVID-19 infection in CRC patients.


Assuntos
Anticarcinógenos/uso terapêutico , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genisteína/uso terapêutico , Fitoestrógenos/uso terapêutico , Atlas como Assunto , COVID-19/imunologia , COVID-19/patologia , COVID-19/virologia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/virologia , Ciclina D1/genética , Ciclina D1/imunologia , Receptores ErbB/genética , Receptores ErbB/imunologia , Humanos , Interleucina-1alfa/genética , Interleucina-1alfa/imunologia , Interleucina-2/genética , Interleucina-2/imunologia , Janus Quinases/genética , Janus Quinases/imunologia , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Terapia de Alvo Molecular/métodos , Família Multigênica , PPAR gama/genética , PPAR gama/imunologia , Farmacogenética/métodos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/imunologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/imunologia , Receptores de Interleucina-6/genética , Receptores de Interleucina-6/imunologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/crescimento & desenvolvimento , SARS-CoV-2/patogenicidade , Fatores de Transcrição STAT/genética , Fatores de Transcrição STAT/imunologia , Transdução de Sinais
16.
Trials ; 22(1): 954, 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34961558

RESUMO

BACKGROUND: Pancreatoduodenectomy is a complex and challenging procedure that requires meticulous tissue dissection and proficient suturing skills. Minimally invasive surgery with the utilization of robotic platforms has demonstrated advantages in perioperative patient outcomes in retrospective studies. The development of robotic pancreatoduodenectomy (RPD) in specific has progressed significantly, since first reported in 2003, and high-volume centers in pancreatic surgery are reporting large patient series with improved pain management and reduced length of stay. However, prospective studies to assess objectively the feasibility and safety of RPD compared to open pancreatoduodenectomy (OPD) are currently lacking. METHODS/DESIGN: The PORTAL trial is a multicenter randomized controlled, patient-blinded, parallel-group, phase III non-inferiority trial performed in seven high-volume centers for pancreatic and robotic surgery in China (> 20 RPD and > 100 OPD annually in each participating center). The trial is designed to enroll and randomly assign 244 patients with an indication for elective pancreatoduodenectomy for malignant periampullary and pancreatic lesions, as well as premalignant and symptomatic benign periampullary and pancreatic disease. The primary outcome is time to functional recovery postoperatively, measured in days. Secondary outcomes include postoperative morbidity and mortality, as well as perioperative costs. A sub-cohort of 128 patients with pancreatic adenocarcinoma (PDAC) will also be compared to assess the percentage of patients who undergo postoperative adjuvant chemotherapy within 8 weeks, in each arm. Secondary outcomes in this cohort will include patterns of disease recurrence, recurrence-free survival, and overall survival. DISCUSSION: The PORTAL trial is designed to assess the feasibility and safety of RPD compared to OPD, in terms of functional recovery as described previously. Additionally, this trial will explore whether RPD allows increased access to postoperative adjuvant chemotherapy, in a sub-cohort of patients with PDAC. TRIAL REGISTRATION: ClinicalTrials.gov NCT04400357 . Registered on May 22, 2020.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Estudos Multicêntricos como Assunto , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do Tratamento
18.
Dig Liver Dis ; 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34903500

RESUMO

BACKGROUND: Liver fibrosis is a common disease that can lead to hepatic failure. AIMS: Our aims were to reveal the role of GAS5 in the regulation of liver fibrosis. METHODS: LX-2 human hepatic satellite cells (HSCs) were cultured and activated using TGF-ß1 treatment. A CCK-8 assay was performed to assess cell viability. A luciferase assay was employed to monitor the interactions between miR-433-3p and GAS5 or toll-like receptor 10 (TLR10). Western blotting and real-time quantitative PCR (RT-qPCR) were applied to detect the expression levels of α-SMA, Col. I, PCNA-, MMP2-, MMP9-, TLR10-, and NF-κB-related molecules at the protein and RNA levels. RESULTS: GAS5 and TLR10 were decreased while miR-433-3p was upregulated in TGF-ß1-activated LX-2 cells. Upregulation of GAS5 or downregulation of miR-433-3p suppressed HSC activation, and luciferase assays indicated that miR-433-3p binds with GAS5 and the 3'-UTR of TLR10. MiR-433-3p upregulation and TLR10 downregulation rescued the impacts of GAS5 overexpression or miR-433-3p knockdown on LX-2 cells. Upregulation of GAS5 also suppressed the phosphorylation of NF-κB through the miR-433-3p/TLR10 axis. CONCLUSION: LncRNA GAS5 exerts an inhibitory effect on HSC activation by suppressing NF-κB signalling through regulation of the miR-433-3p/TLR10 axis.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34899943

RESUMO

The low adverse effects of acupuncture for primary dysmenorrhea (PD), known as one of the most commonly reported gynecological debilitating conditions affecting women's overall health, have been thus far confirmed. Moreover, it has been increasingly recognized that inflammation is involved in such menstrual cramps, and recent studies have further shown that the anti-inflammatory effects of acupuncture are helpful in its control. This review portrays the role of inflammation in PD pathophysiology, provides evidence from clinical and animal studies on acupuncture for inflammation-induced visceral pain, and reflects on acupuncture-related therapies for dysmenorrhea with regard to their anti-inflammatory characteristics. Further research accordingly needs to be carried out to clarify the effects of acupuncture on proinflammatory factors in PD, particularly chemokines and leukocytes. Future studies on this condition from an anti-inflammatory perspective should be also performed in line with the notion of emphasizing stimulation modes to optimize the clinical modalities of acupuncture. Additionally, the effects and mechanism of more convenient self-healing approaches such as TENS/TEAS for PD should be investigated.

20.
Front Oncol ; 11: 694664, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34900664

RESUMO

The last decade has witnessed revolutionary advances taken in immunotherapy for various malignant tumors. However, immune-related molecules and their characteristics in the prediction of clinical outcomes and immunotherapy response in clear cell renal cell carcinoma (ccRCC) remain largely unclear. C-C Motif Chemokine Ligand 4 (CCL4) was extracted from the intersection analysis of common differentially expressed genes (DEGs) of four microarray datasets from the Gene Expression Omnibus database and immune-related gene lists in the ImmPort database using Cytoscape plug-ins and univariate Cox regression analysis. Subsequential analysis revealed that CCL4 was highly expressed in ccRCC patients, and positively correlated with multiple clinicopathological characteristics, such as grade, stage and metastasis, while negatively with overall survival (OS). We performed gene set enrichment analysis (GSEA) and gene set variant analysis (GSVA) with gene sets coexpressed with CCL4, and observed that gene sets positively related to CCL4 were enriched in tumor proliferation and immune-related pathways while metabolic activities in the negatively one. To further explore the correlation between CCL4 and immune-related biological process, the CIBERSORT algorithm, ESTIMATE method, and tumor mutational burden (TMB) score were employed to evaluate the tumor microenvironment (TME) characteristics of each sample and confirmed that high CCL4 expression might give rise to high immune cell infiltration. Moreover, correlation analysis revealed that CCL4 was positively correlated with common immune checkpoint genes, such as programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), and lymphocyte activating 3 (LAG3). Overall, this study demonstrated that CCL4 might serve as a potential immune-related prognostic biomarker to predict clinical outcomes and immunotherapy response in ccRCC. Moreover, CCL4 might contribute to TME modulation, indicating the mechanism CCL4 involved in tumor proliferation and metastasis, which could provide novel therapeutic perceptions for ccRCC patients.

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